Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome

• DOI: 10.1016/j.celrep.2024.113935
• Publication Date: 2024-03-07T21:57:02Z
• Authors: Elizabeth R. Barrow; Evelina Valionyte; Chris R. Baxter; Yi Yang; Sharon Herath; William A. O’Connell; Justyna Lopatecka; Alexander Strachan; Waldemar Woznica; Holly N. Stephenson; Gyorgy Fejer; Vikram Sharma; Boxun Lu; Shouqing Luo
• Keywords: Inflammation; 0301 basic medicine; 03 medical and health sciences; QH301-705.5; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Sequestosome-1 Protein; Autophagy; Humans; CP: Molecular biology; Biology (General); Processing Bodies

Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) stress represent vital responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known play critical roles in selective autophagy; however, it is unknown whether p62 can exist another form addition its autophagic droplets. Here, we found that, under conditions, including proteotoxicity, endotoxicity, oxidation, transformed a type of enlarged PBs, termed p62-dependent (pd-PBs). phase separation essential for the nucleation pd-PBs. Mechanistically, pd-PBs triggered by enhanced droplet formation upon stimulation through interactions between DDX6, DEAD-box ATPase. Functionally, recruit NLRP3 inflammasome adaptor ASC assemble induce inflammation-associated cytotoxicity. Our study shows that droplet-to-PB transformation acts response activate process, suggesting persistent lead NLRP3-dependent inflammation toxicity.